Chemically assembled nano-scale circuit elements

ABSTRACT

The present invention provides nano-scale devices, including electronic circuits, using DNA molecules as a support structure. DNA binding proteins are used to mask regions of the DNA as a material, such as a metal is coated onto the DNA. Included in the invention are DNA based transistors, capacitors, inductors and diodes. The present invention also provides methods of making integrated circuits using DNA molecules as a support structure. Methods are also included for making DNA based transistors, capacitors, inductors and diodes.

The present application is a continuation-in-part and claims the benefitof U.S. patent application Ser. No. 09/315,750 filed on May 20, 1999 nowU.S. Pat. No. 6,248,529, which claims the benefit of U.S. ProvisionalPatent Applications Serial Nos. 60/086,163, filed May 20, 1998, and60/095,096, filed Aug. 3, 1998.

BACKGROUND OF THE INVENTION

Computer chip design has improved at a rapid pace. According to Moore'slaw, the number of switches which can be produced on a computer chip hasdoubled every 18 months. Chips now can hold millions, of transistors.However, it is becoming increasingly difficult to increase the number ofelements on a chip using present technologies. At the present rate, inthe next few years the theoretical limit of silicon based chips will bereached. Since, the data storage and processing capabilities ofmicrochips are determined by the number of elements which can bemanufactured on a chip, new technologies are required which will allowfor the development of higher performance chips.

Present chip technology is also limiting when wires need to be crossedon a chip. For the most part, the design of a computer chip is limitedto two dimensions. Each time a circuit must cross another circuit,another layer must be added to the chip. This increases the cost anddecreases the speed of the resulting chip.

A number of alternatives to standard silicon based complementary metaloxide semiconductor (“CMOS”) devices have been proposed, includingsingle electron transistors, quantum cellular automata, neural networks,and molecular logic devices. (Chen et al., Appl. Phys. Lett. 68:1954(1996); Tougaw, et al, J. Appl. Phys. 75:181 (1994); Caldwell, et al.,Science 277:93 (1997); Mead, Proc. IEEE 78:1629 (1990); Hopfiled, etal., Science 233:625 (1986); Aviram, et al., Chem. Phys. Lett. 29:277(1974); and Petty et al. Eds., Introduction to Molecular Electronics(Edward Arnold, London, 1995)). The common goal is to produce logicdevices on a nanometer scale. Such dimensions are more commonlyassociated with molecules than integrated circuits.

DNA molecules has recently been used as a support structure for theformation of 100 nanometer scale silver wires (Braun et al.,“DNA-Templated Assembly and Electrode Attachment of a Conducting SilverWire,” Nature 391:775-78 (1998); PCT Application WO 99/04440, which arehereby incorporated by reference). Furthermore, the DNA molecule allowsfor specific targeting of the end of the DNA-wire to complimentarynucleotide sequences on a chip. The reduced size of these wires allowsfor a lower level of voltage to be used in a circuit, decreasesoperating temperatures and magnetic field strength, and faster circuits.

Integrated circuits on computer chips require numerous structuresincluding, resistors, capacitors, and transistors. Therefore, thereduction of wiring to the 100 nanometer level may somewhat reduce thesize of integrated circuits but the improvements are limited by the sizeof the other components.

Nucleic acid molecule directed assembly is also advantageous because itcan direct the synthesis of three dimensional structures. Inductors cannot be constructed on conventional chips, because they are threedimensional structures. Molecular biology provides tools formanipulating nucleic acid molecules at the molecular level. Nucleic acidmolecules also provide other advantages, since nucleic acid moleculescan be rapidly replicated with high fidelity using existingtechnologies. Furthermore, nucleic acid molecules can store informationin their structure which can be used to direct the formation of complexcircuits.

“DNA computers” have also been described recently in the literature inwhich computation occurs via chemical reactions. (Adelman, Science266:1021 (1994), which is hereby incorporated by reference). This methodhas limited usefulness, because the nucleic acid molecules must besynthesized, reacted together, and the appropriate “result” must beisolated and sequenced. Thus, it is unclear how this technology could beused for everyday applications.

Therefore, new methods of fabricating integrated circuit components areneeded, where elements of an integrated circuit can be manufactured on anano scale. Furthermore, a need exists for taking advantage of theinformation coding capabilities of DNA in the formation of integratedcircuits.

SUMMARY OF THE INVENTION

The present invention provides a method of masking a region of a nucleicacid molecule by binding a nucleic acid binding molecule to a bindingsite on the nucleic acid molecule, coating the non-protected portions ofthe nucleic acid molecule with a material, and removing the nucleic acidbinding molecule from the nucleic acid molecule.

A method of manufacturing a nano-scale device using a nucleic acidmolecule as a template is also provided by providing a nucleic acidmolecule template, protecting a region or regions of the template usinga nucleic acid binding molecule, coating the unprotected regions with afirst material, removing the nucleic acid binding molecule, and coatingthe unprotected and uncoated regions of the template with a secondmaterial to form a nano-scale device.

A method of manufacturing a circuit element using a nucleic acidmolecule as a template is also provided by providing a nucleic acidmolecule template, protecting a region or regions of the template usinga nucleic acid binding molecule, coating the unprotected regions with afirst material, removing the nucleic acid binding molecule, and coatingthe unprotected and uncoated regions of the template with a secondmaterial to form a circuit element, where the second electricallyconductive or insulating material is different from the first secondelectrically conductive or insulating material.

A further embodiment of the present invention is a circuit elementhaving a nucleic acid template where two or more regions of the templateare coated with different materials.

The invention also provides a resistor, a capacitor, an inducer, and atransistor each having a nucleic acid molecule template.

Yet another embodiment of the invention is a method of forming a circuitelement by applying a semiconductor to a nucleic acid molecule.

Another embodiment of the invention is a circuit element with a nucleicacid template where two or more regions of the template are coated withdifferent materials.

Another embodiment of the invention is a resistor having a firstmaterial separated by a second material. The second material has adifferent resistivity than the first material and the first and secondmaterials having a common nucleic acid template core.

Another embodiment of the invention is a resistor with at least oneresistive material and a pair of at least partially conductive leads.Each of the leads is coupled to the resistive material and the resistivematerial and the pair of leads have a nucleic acid template core.

Yet another embodiment of the invention is a diode with a first type ofsemiconductor material adjacent to a second type of semiconductormaterial. The first and second types of semiconductor materials have acommon nucleic acid template core.

Yet another embodiment of the invention is a diode with a first type ofsemiconductor material adjacent to second type of semiconductor materialand a pair of at least partially conductive leads. Each of the leads iscoupled to one of the first and second types of semiconductor materialsand the first and second types of semiconductor materials and the pairof leads have a nucleic acid template core.

A further embodiment of the invention is a capacitor with a pair of atleast partially conductive plates separated by a dielectric where eachof the plates has a nucleic acid template core.

A further embodiment of the invention is a capacitor with a pair of atleast partially conductive plates separated by a dielectric where thedielectric has a nucleic acid template core. Yet another embodiment ofthe invention is a transistor comprising a first type of semiconductormaterial separated by a second type of semiconductor material.

The first and second types of semiconductor materials have a commonnucleic acid template core.

Yet another embodiment of the invention is transistor with a second typeof semiconductor material separating a first type of semiconductormaterial. Each of a plurality of at least partially conductive leads iscoupled to one of the first and second types of semiconductor materials.The first and second types of semiconductor materials and the leads havea nucleic acid template core.

A further embodiment of the invention is an inducer with a coil of atleast partially conductive material where the coil has a nucleic acidtemplate core.

Another embodiment of the invention is a method for making a resistor.The method includes: protecting at least one region of a nucleic acidmolecule template using a nucleic acid binding molecule; coatingunprotected regions of the nucleic acid molecule template with a firstconductive material; removing the nucleic acid binding molecule from theprotected region; and coating the protected region with a secondconductive material, where the second conductive material has adifferent resistivity from the first conductive material.

Another embodiment of the invention is a method for making a diode. Themethod includes: protecting at least one region of a nucleic acidmolecule template using two or more nucleic acid binding molecules;coating unprotected regions of the nucleic acid molecule template with aconductive material; removing at least one of the nucleic acid bindingmolecules from a one portion of the protected region; coating the oneportion of the protected region with a first-type of semiconductormaterial; removing any remaining ones of the nucleic acid bindingmolecules from any remaining portion of the protected region; coatingthe remaining portion of the protected region with a second type ofsemiconductor material.

Yet another embodiment of the invention is a method for making acapacitor. The method includes coating parallel regions of a nucleicacid molecule template with a conductive material where each of thecoated parallel regions is coupled to a lead.

Yet another embodiment of the present invention is another method formaking a capacitor. The method includes: protecting a dielectric regionof a nucleic acid molecule template between parallel regions of anucleic acid molecule template with at least one nucleic acid bindingmolecule; coating unprotected parallel regions of the nucleic acidmolecule template around the dielectric region with a conductivematerial; removing the nucleic acid binding molecule from the dielectricregion; and coating the dielectric region with a dielectric material.

A further embodiment of the invention is a method for making atransistor. The method includes: protecting a central region and two ofthree adjacent branch regions of a nucleic acid molecule template withnucleic acid binding molecules; coating unprotected regions of thenucleic acid molecule template with a conductive material; removing theone or more nucleic acid binding molecules protecting the central regionof the nucleic acid molecule template; coating the central region with afirst-type of semiconductor material; removing the nucleic acid bindingmolecules from the protected branch regions; and coating the branchregions with a second type of semiconductor material.

Yet another embodiment of the invention is a method for making aninducer. The method includes wrapping a nucleic acid molecule templatearound at least one protein and coating the nucleic acid moleculetemplate with a first conductive material.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a method for the assembly of a circuit element usingmasking proteins.

FIG. 2 shows how the method of the present invention can be used toproduce a nanometer scale diode.

FIG. 3A-3G show how the method of the present invention can be used toproduce a nanometer scale transistor.

FIG. 4 shows an inducer produced by the present invention. The wire isdeveloped around histone-like proteins which hold the nucleic acidtemplate in a coiled configuration.

FIG. 5 shows a capacitor produced by the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods for manufacturing nano-scaledevices, including circuit elements using a nucleic acid molecule as atemplate. The sequence of the nucleic acid molecule is used to directthe formation of the device. Nucleic acid molecule binding proteins ornucleic acids can be used to protect regions of the nucleic acidmolecule, masking it for the later deposition of desired coating metalsor other substrates.

Devices can be assembled either by forming a complete DNA templatestructure and then applying the coating materials in one or more stepsor by assembling various subunits of the device and then assembling thesubunits into a single device. The present invention is well suited forassembly of subunits by providing a method for protecting exposed DNAtags which can then direct the assembly of the subunits. Homologous tagsare used to join subunits at the desired location.

In a preferred embodiment of the invention, the device consists of anelectronic circuit. However, the method of the present invention can beused to direct the formation of any nano-scale structure, includingmechanical and structural elements.

Circuits refers to any assembly of one or more circuit elements. Theterms integrated circuit or electronic circuit are used interchangeablywith circuit within this application. The methods of the presentinvention can be used to produce extremely small scale circuit elementswhich can in turn be used to produce logic circuits. Therefore, thepresent invention is applicable for the synthesis of relatively simpleelectronic circuits comprising just a few elements up to the synthesisof complicated computer circuits with millions of circuit elements.

The present invention provides for the chemical assembly of integratedcircuits. A method is provided which allows the chemical synthesis ofvarious electronic components, e.g. wires, switches, and memoryelements. The method also allows for the self-ordering of the electroniccomponents into a working computer or electronic circuit. The presentinvention relies on biologically directed chemical assembly, but theoperation of the circuit is electronic.

The present invention provides a method of masking a region of a nucleicacid molecule by binding a nucleic acid binding molecule to a bindingsite on the nucleic acid molecule, coating the non-protected portions ofthe nucleic acid molecule with a material, and removing the nucleic acidbinding molecule from the nucleic acid molecule.

A method of manufacturing a circuit element using a nucleic acidmolecule as a template is also provided by providing a nucleic acidmolecule template, protecting a region or regions of the template usinga nucleic acid binding molecule, coating the unprotected regions with afirst material, removing the nucleic acid binding molecule, and coatingthe unprotected and uncoated regions of the template with a secondmaterial to form a circuit element, where the second electricallyconductive or insulating material is different from the first secondelectrically conductive or insulating material.

The method of manufacturing a circuit element may further consist ofdisrupting or removing the DNA template from the circuit or a portionthereof. Nucleic acid molecules have intrinsic electric properties,which may interfere with the functioning of certain circuit elements.One may take into account the electrical properties of the nucleic acidmolecule in the design of the element. Where it is not possible toincorporate the intrinsic properties of the nucleic acid molecule intothe circuit element, it may be preferred to disrupt or remove thenucleic acid molecule or a portion of the molecule.

In addition to applying the material to the nucleic acid molecule. Acoating material may be applied over the material to prevent coating ofthe first material by later applied materials. Such a coating may bepermanent or may be removed at a later stage in the processing of thecircuit.

By carefully choosing the sequence of the nucleic acid template and thebinding proteins to be used, large and complicated circuits can beassembled in solution. The self-assembling nature of the circuits wouldallow for the rapid and inexpensive formation of complicated circuits.Even if there is some lack of fidelity, functional circuits could betested for and selected for further use. More complicated structures canbe manufactured using combinations of nucleic acid binding compounds.

Various combinations of proteins or nucleic acids can be used to protectthe nucleic acid molecule. The choice of the protecting molecule will bemade based upon the size of the region to be protected and the bindingaffinity of the protecting molecule. After applying a metal or othersubstrate to the nucleic acid molecule template, some or all of theprotecting proteins are removed from the nucleic acid molecule.Additional rounds of protecting the nucleic acid molecule with bindingmolecules and subsequent coating can be carried out to create variouscircuit elements.

In the present invention, preferred nucleic acid molecules include RNAand DNA. Also included within the invention are chemically modifiednucleic acid molecules or nucleic acid analogs. Such RNA or DNA analogscomprise but are not limited to 2′-O-alkyl sugar modifications,methylphosphonate, phosphorothioate, phosphorodithioate, formacetal,3′-thioformacetal, sulfone, sulfamate, and nitroxide backbonemodifications, amides, and analogs wherein the base moieties have beenmodified. In addition, analogs of oligomers may be polymers in which thesugar moiety has been modified or replaced by another suitable moiety,resulting in polymers which include, but are not limited to, polyvinylbackbones (Pitha et al., “Preparation and Properties of Poly(I-vinylcytosine),” Biochim Biophys Acta 204:381-8 (1970); Pitha et al.,“Poly(1-vinyluracil): The Preparation and Interactions with AdenosineDerivatives,” Biochim Biophys Acta 204:39-48 (1970), which are herebyincorporated by reference), morpholino backbones (Summerton, et al.,“Morpholino Antisense Oligomers: Design, Preparation, and Properties,”Antisense Nucleic Acid Drug Dev 7:187-9 (1997) and peptide nucleic acid(PNA) analogs (Stein et al., “A Specificity Comparison of Four AntisenseTypes: Morpholino, 2′-O-methyl RNA, DNA, and Phosphorothioate DNA,” J.Antisense Nucleic Acid Drug Dev. 7:151-7 (1997); Egholm, et al. PeptideNucleic Acids (PNA)-Oligonucleotide Analogues with an Achiral PeptideBackbone, (1992); Faruqi et al., “Peptide nucleic acid-targetedmutagenesis of a chromosomal gene in mouse cells,” Proc. Natl. Acad.Sci. USA 95:1398-403 (1998); Christensen, et al. “Solid-Phase Synthesisof Peptide Nucleic Acids,” J. Pept. Sci. 1:175-83 (1995); Nielsen etal., “Peptide Nucleic Acid (PNA). A DNA Mimic with a Peptide Backbone,”Bioconjug. Chem. 5:3-7 (1994), which are hereby incorporated byreference). In addition linkages may contain the following exemplarymodifications: pendant moieties, such as, proteins (including, forexample, nucleases, toxins, antibodies, signal peptides andpoly-L-lysine); intercalators (e.g., acridine and psoralen), chelators(e.g., metals, radioactive metals, boron and oxidative metals),alkylators, and other modified linkages (e.g., alpha anomeric nucleicacids). Such analogs include various combinations of the above-mentionedmodifications involving linkage groups and/or structural modificationsof the sugar or base for the purpose of improving RNAseH-mediateddestruction of the targeted RNA, binding affinity, nuclease resistance,and or target specificity.

Various combinations of proteins or nucleic acids can be used to protectthe nucleic acid molecule. The choice of the protecting molecule will bemade based upon the size of the region to be protected and the bindingaffinity of the protecting molecule. After applying a metal or othersubstrate to the nucleic acid molecule template, some or all of theprotecting proteins are removed from the nucleic acid molecule.Additional rounds of protecting the nucleic acid molecule with bindingmolecules and subsequent coating can be carried out to create variouscircuit elements.

Nucleic acid molecules can be used to form a complex support structures,including three dimensional structures (Chen et al., “Synthesis from DNAof a Molecule with the Connectivity of a Cube,” Nature 350:631-633(1991), which is hereby incorporated by reference). Because of theself-assembling nature of complimentary nucleic acid molecules, complexstructures can be assembled in one reaction. Methods for the making andmanipulation of nucleic acid molecules, including synthesis, ligation,restriction, modification, hybridization and separation can be found inShort Protocols in Molecular Biology, A Compendium of Methods fromCurrent Protocols in Molecular Biology, Ausubel, F. M., et al., editors,2nd Edition, Green Publishing Associates and John Wiley and Sons, NewYork (1992); Sambrook et al., Molecular Cloning: a Laboratory Manual,Cold Spring Harbor, N.Y., Cold Spring Harbor Laboratory, (1989), whichare hereby incorporated by reference.

Directed formation of the nucleic acid support structure is carried outby sequence specific hybridization (Short Protocols in MolecularBiology, A Compendium of Methods from Current Protocols in MolecularBiology, Ausubel, F. M., et al., editors, 2nd Edition, Green PublishingAssociates and John Wiley and Sons, New York (1992); Sambrook et al.,Molecular Cloning: a Laboratory Manual, Cold Spring Harbor, N.Y., ColdSpring Harbor Laboratory, (1989), which are hereby incorporated byreference). A large circuit may be formed in one step or in multiplehybridization steps, where subunit portions of the support are assembledat a later stage. Hybridization conditions can be determined usingformulas well known in the art (See Southern, et al., J. Mol. Biol.,98:503-517 (1979), which is hereby incorporated by reference).

Native nucleic acid molecules, as well as modified nucleic acids, mayform triple or four stranded arrangements which can be used Bringtogether three or more leads (Footer, et al. “Biochemical Evidence thata D-loop is Part of a Four-Stranded PNA-DNA Bundle. Nickel-MediatedCleavage of Duplex DNA by a Gly-Gly-His bis-PNA,” Biochemistry 35(33):10673-9 (1996), which is hereby incorporated by reference).

Suitable nucleic acid molecules can be made synthetically. A preferredmethod for manufacturing synthetic nucleic acid molecules is thestandard phosphoramidite chemistry method using either an AppliedBiosystems 380B or a Milligen 7500 automated DNA synthesizer (Van Nesset al., Nucl. Acids Res. 19:3345-3350 (1991); Van Ness et al, Nucl.Acids Res. 19:5143-5151 (1991), which are hereby incorporated byreference).

Alternatively, portions of the structure may be assembled independentlyand the resulting parts assembled into the final structure, eitherbefore or after coating the nucleic acid molecules. Post-coatingassembly may be facilitated by protecting the portions of the nucleicacid molecules, which will hybridize to the other parts, with nucleicacid binding proteins. These proteins may be removed prior toself-assembly of the final structure.

Once isolated or synthesized, multiple copies of the nucleic acidmolecules may be prepared using PCR technology (Kawasaki, 1990, PCRProtocols: A Guide to Methods and Applications, Innis et al. eds.Academic Press, San Diego; and Wang and Mark, PCR Protocols: A Guide toMethods and Applications, Innis et al. eds. Academic Press, San Diego(1990), which is hereby incorporated by reference).

In addition to building a scaffold or support for the circuit out ofnucleic acids, other materials may also be used. Nucleic acids can beattached to particles or chips to support the formation and stability ofthe circuit (Mirkin et al., “A DNA-Based Method for RationallyAssembling Nanoparticles into Macroscopic Materials,” Nature 382:607-611(1996); Fodor et al., U.S. Pat. No. 5,445,934, “Array ofOligonucleotides on a solid surface” (1995), which is herebyincorporated by reference).

After hybridization, the stability of the structure may be increased byligation of breaks in the molecules (Stryer, Biochemistry 2^(nd) Ed., W.H. Freeman & Co., (1975), which is hereby incorporated by reference).

Restriction endonucleases can be used to break unwanted connections. Forexample, some fragments may be used to assist in the formation of thefinal structure but may not be needed in the final structure. Therefore,after formation of the structure, restriction endonucleases may be usedto remove those fragments which are not desired in the final structure.

Nucleic acids produced by PCR or synthesis must be carefully produced tomaintain fidelity. Fidelity may be improved by including a mismatchrepair system. For example including the mut mismatch repair enzymesfrom Escherichia coli. Fidelity may also be affected by varyingtemperature and salt conditions. In a preferred method, high fidelitypolymerases or mutant polymerases are utilized to ensure the fidelity ofnucleic acid replication.

Alternatively, naturally occurring nucleic acid molecules may beselected and isolated from living organisms, including viruses,bacteria, plants and animals. Desired nucleic acids may be isolated fromthe organisms using methods known to those skilled in the art. Forexample, natural sequences may be amplified and isolated using PCRtechnology. Preferred naturally occurring sequences would includeregions upstream of genes which consist of promoter or enhancerelements. Such regions would be rich in binding sites for nucleic acidmolecule binding proteins.

The nucleic acid molecules may also be modified, to facilitate coatingof the nucleic acid molecule at improved levels or with a wider varietyof materials. For example, analogues of the common deoxyribo- andribonucleosides which contain amino groups at the 2′ or 3′ position ofthe sugar can be made using established chemical techniques. (See,Imazawa et al., J. Org. Chem. 44:2039 (1979); Imazawa et al., J. Org.Chem. 43(15):3044 (1978); Verheyden et al., J. Org. Chem. 36(2):250(1971); Hobbs et al., J. Org. Chem. 42(4):714 (1977), which are herebyincorporated by reference). In addition, oligonucleotides may besynthesized with 2′-5′ or 3′-5′ phosphoamide linkages (Beaucage et al.,Tetrahedron 49(10):1925 (1992); Letsinger, J. Org. Chem. 35:3800 (1970);Sawai, Chem. Left. 805 (1984); F. Eckstein, Ed., Oligonucleotides andAnalogues: A Practical Approach (Oxford University Press 1991), whichare hereby incorporated by reference).

Amplification of a selected, or target, nucleic acid sequence may becarried out by any suitable means. (See generally Kwoh, D. and Kwoh, T.,Am Biotechnol Lab, 8, 14 (1990) which is hereby incorporated byreference.) Examples of suitable amplification techniques include, butare not limited to, polymerase chain reaction, ligase chain reaction(see Barany, Proc Natl Acad Sci USA 88, 189 (1991), which is herebyincorporated by reference), strand displacement amplification (seegenerally Walker, G. et al., Nucleic Acids Res. 20, 1691 (1992); Walker.G. et al., Proc Natl Acad Sci USA 89, 392 (1992), which are herebyincorporated by reference), transcription-based amplification (see Kwoh,D. et al., Proc Natl Acad Sci USA, 86, 1173 (1989), which is herebyincorporated by reference), self-sustained sequence replication (or“3SR”) (see Guatelli, J. et al., Proc Natl Acad Sci USA, 87, 1874(1990), which is hereby incorporated by reference), the Qb replicasesystem (see Lizardi, P. et al., Biotechnology, 6, 1197 (1988), which ishereby incorporated by reference), nucleic acid sequence-basedamplification (or “NASBA”) (see Lewis, R., Genetic Engineering News,12(9), 1 (1992), which is hereby incorporated by reference), the repairchain reaction (or “RCR”) (see Lewis, R., Genetic Engineering News,12(9), 1 (1992), which is hereby incorporated by reference), andboomerang DNA amplification (or “BDA”) (see Lewis, R., GeneticEngineering News, 12(9), 1 (1992), which is hereby incorporated byreference). Polymerase chain reaction is currently preferred.

In general, DNA amplification techniques such as the foregoing involvethe use of a probe, a pair of probes, or two pairs of probes whichspecifically bind to the nucleic acid molecule of interest, but do notbind to other nucleic acid molecules which are not desired, under thesame hybridization conditions, and which serve as the primer or primersfor the amplification of the nucleic acid molecule of interest or aportion thereof in the amplification reaction.

The sequence of the templates can be verified by sequencing themolecules by either chemical (Maxam et al., Proc. Nat'l Acad. Sci. USA,74:560 (1977), which is hereby incorporated by reference) or enzymaticmethods (Sanger, et al., Proc. Nat'l Acad. Sci. USA, 74:5463 (1977),which is hereby incorporated by reference).

The nucleic acid molecule itself may have some conductive properties ofits own. These properties may be modified to reduce any detrimentaleffects on the function of the electronic circuit (Meade, et al, U.S.Pat. No. 5,770,369, “Nucleic Acid Mediated Electron Transfer” (1998),which is hereby incorporated by reference). Modification of theelectrical properties of the nucleic acid molecule may be made byintercalating compounds between the bases of the nucleic acid molecule,modifying the sugar-phosphate backbone, or by cleaving the nucleic acidmolecule after the circuit elements are formed. Cleavage of the nucleicacid molecule may be accomplished by irradiation, chemical treatment, orenzymatic degradation. Irradiation using gammaradiation is preferredbecause radiation may penetrate materials coating the nucleic acidmolecule.

In another embodiment of the invention, one strand of a double strandednucleic acid molecule is modified to decrease or inhibit coating of thatstrand. The coated nucleic acid molecule would then be coated on onlyone side, allowing for the chemical or enzymatic removal of the nucleicacid template after the formation of the circuit elements.

Masking of nucleic acids from coating can be carried out with nucleicacid binding proteins, nucleic acid molecules, antibodies, or othercompounds which can interact stablely with the nucleic acid molecule andblock access to the nucleic acid molecule. In a preferred embodiment ofthe invention, nucleic acid binding proteins are used to protect thenucleic acid molecule from coating.

Nucleic acid binding molecules may be sequence preferential or sequencespecific. Sequence-preferential binding refers to nucleic acid bindingmolecules that generally bind nucleic acid molecules but that showpreference for binding to some sequences over others.Sequence-preferential binding is typified by small molecules, e.g.,distamycin. Many nucleic acid binding molecules are known and theirinteractions with the nucleic acid molecules have been studied. (Seee.g., Boulikas, “A Compilation and Classification of DNA Binding Sitesfor Protein Transcription Factors from Vertebrates,” Crit. Rev. Eukavot.Gene Expr. 4:117-321 (1994), which is hereby incorporated by reference).Such nucleic acid molecules include transcriptional and translationalactivators, repair enzymes, histones, ligases, restriction nucleases,etc.

The available nucleic acid binding proteins number in the hundreds. Inaddition, modified or mutant binding proteins increase the number ofavailable proteins for use in the present invention. Selection of theappropriate nucleic acid binding protein will be based upon a number offactors. Among the more significant factors, the size of the regionprotected by the binding protein will determine the protein to be used.The electrical function of an element will often be dependent upon thelength of the element. Thus the size of the protected region isimportant in creating an element with the desired properties. Someproteins may also form multimers more readily for protecting largerregions of the nucleic acid molecule. Another factor to be consideredwhen choosing a binding protein is the affinity of the protein for itstarget sequence. A higher affinity may be useful for decreasing thefrequency of malformed elements. On the other hand, the affinity shouldbe at a level where the binding protein can be effectively removed whenneeded. Since several different proteins will be needed in theproduction of more complex circuits, the compatibility of the variousproteins will also be a factor. Proteins are desired which can beremoved effectively, without affecting the protection by the otherbinding proteins being used.

Ligases can be utilized to increase the stability of the DNA templateafter the fragments have been allowed to hybridize. Ligation will makethe structure more resistant to denaturation by heat or salt in furthersteps.

In addition, endo or exo-nucleases may be used to remove portions of thesupport structure when they are no longer needed. Nucleic acid moleculesmay be used to hold parts of the structure in place during coating andthen removed later.

Preferred nucleic acid binding molecules are regulatory molecules. Inparticular, the lac and the repressor proteins have been well studied.The lactose repressor protein may be prepared as described in theliterature: Rosenberg, J. M. et al., Nucleic Acid Res. 4(3):567 (1977);Matthews, K. S., J. Biol. Chem. 253(12):4279 (1978); O'Gorman, R. B. etal., J. Biol. Chem. 255(21):10100 (1980); Levens, D. and P. M. Howley,Mol. Cell. Biol. 5(9):2307 (1985), which are hereby incorporated byreference. The presence, activity and degree of purity of the lactoserepressor protein prepared using the above referenced methods can bedetermined using procedures described in the literature. (Bourgeois, S.and A. D. Riggs, Biochem. Biophys. Res. Comm. 38(2):348 (1970); Barkley,M. D. and S. Bourgeois in The Operon, Cold Spring Harbor, N.Y. pp.177-220 (1978); and Bourgeois, S. in Methods in Enzymology Vol. 21, pp.491-500 (1971), which are hereby incorporated by reference).

The tetracycline (tet) repressor protein may be prepared as described inthe literature: Hillen et al., J. Mol. Biol. 257(11):6605 (1982);Oehmichen et al., EMBO J. 3(3):539 (1984), which are hereby incorporatedby reference. The tet repressor protein may be assayed and characterizedas described by: Altschemied et al., J. Mol. Biol. 187:341 (1986);Hillen et al., J. Mol. Biol. 172:185 (1984); Hillen et al., J. Mol.Biol. 169:707 (1983), which are hereby incorporated by reference.

Also preferred are restriction endonucleases. Proteins such asrestriction nucleases have well known binding sequences. However, thenuclease activity may not be desired. Appropriate buffer conditions maybe used to facilitate binding to the nucleic acid but prevent cleavageof the template molecule. Similarly, other proteins may requirecofactors for activity and thus undesired activities may be regulated byomitting necessary cofactors. (Chiang et al., “Effects of Minor GrooveBinding Drugs on the Interaction of TATA Box Binding Proteins and TFIIAwith DNA,” Biochemistry 33:7033-40 (1994); Wu et al., “Physical andFunctional Sensitivity if Zinc Finger Transcription Factors to RedoxChange,” Mol. Cell. Biol. 16:1035-46 (1996); Aranyi et al.,“Gluccocorticoid Receptor is Activated by Heparin and Deactivated byPlasmin,” Acta Biochem. Biophy. Acad. Sci. Hung. 20:129-33 (1985);Ralston et al., “Metalloregulatory Proteins and molecular Mechanisms ofHeavy Metal Signal Transduction,” Adv. Inorg. Biochem. 8:1-31 (1990);Pratt, “Transformation of Gluccocorticoid and Progesterone Receptors tothe DNA-Binding State,” J. Cell Biochem. 35:51-68 (1987), which arehereby incorporated by reference). Alternatively, mutant forms ofrestriction endonucleases can be utilized which lack nuclease activitybut maintain the sequence specific binding activity.

Fragments of nucleic acid binding proteins may also be used if theycontain the functional nucleic acid binding domain. These fragments mayhave smaller footprints and therefore may be useful in varying the sizeof the protected region. Methods for identifying and isolating functionnucleic acid binding fragments are known in the art (Sukhatme et al.,U.S. Pat. No. 5,773,583, “Methods and Materials Relating to theFunctional Domains of DNA Binding Proteins,” (1998), which is herebyincorporated by reference).

Hybrid proteins can also be utilized to prepare nucleic acid-bindingproteins of interest. Such hybrid proteins can be isolated by affinityor immunoaffinity columns. Further, DNA-binding proteins can be isolatedby affinity chromatography based on their ability to interact with theircognate DNA binding site. Alternatively, other expression systems inbacteria, yeast, insect cells or mammalian cells can be used to expressadequate levels of a nucleic acid-binding protein for use in this assay.

Mutant binding proteins also may be used. Mutations in binding proteinsmay result in changes in sequence specificity or affinity.

Any protein that binds to a specific recognition sequence may be usefulin the present invention. One constraining factor is the effect of theimmediately adjacent sequences (the test sequences) on the affinity ofthe protein for its recognition sequence. Nucleic acid molecule:proteininteractions in which there is little or no effect of the test sequenceson the affinity of the protein for its cognate site are preferable foruse in the described assay; however, nucleic acid molecule:proteininteractions that exhibit (test sequence-dependent) differential bindingmay still be useful if algorithms are applied to the analysis of datathat compensate for the differential affinity. In general, the effect offlanking sequence composition on the binding of the protein is likely tobe correlated to the length of the recognition sequence for theDNA-binding protein. Generally, the kinetics of binding for proteinswith shorter recognition sequences are more likely to suffer fromflanking sequence effects, while the kinetics of binding for proteinswith longer recognition sequences are more likely to not be affected byflanking sequence composition.

The region, which is protected by a single nucleic acid binding protein,may be limited. However, multiple nucleic acid molecule binding proteinscan be used to protect larger regions of the nucleic acid molecule.Indeed, some nucleic acid binding proteins, have protein-proteininteractions, which facilitate the protection of large regions ofnucleic acid molecules. A mixture of different binding domains can beused to set the exact length to be protected.

The concentration of the nucleic acid binding proteins is important. Asone nucleic acid:protein complex dissociates, the released nucleic acidrapidly reforms a complex with another protein in solution. Since theprotein is in excess to the nucleic acid, dissociations of one complexalways result in the rapid reassociation of the nucleic acid intoanother nucleic acid:protein complex. At equilibrium, very few nucleicacid molecules will be unbound. If the unbound nucleic acid is thecomponent of the system that is measured, the minimum background of theassay is the amount of unbound nucleic acid observed during any givenmeasurable time period.

Removing the masking proteins from the nucleic acid molecule can be doneusing methods known to those skilled in the art for removing bindingproteins from nucleic acids.

Some nucleic acid binding proteins, especially transcriptional andtranslational activators or repressors depend upon cofactors for theirability to bind to or release from a nucleic acid molecule. Thus, byadding or removing co-factors from the solution. The binding of maskingproteins could be carefully regulated.

Proteins are also subject to denaturation by chemicals which do noteffect the nucleic acids. For example, phenol and chloroform can be usedto strip proteins from nucleic molecules without affecting the nucleicacid molecule itself.

In another method would be to increase the salt concentration of thesolution surrounding the circuit. By altering the salt concentrationproteins could be stripped off the nucleic acids. Moreover, by usingproteins with binding coefficients having different sensitivities tosalt, some proteins could be removed from the nucleic acid templatewhile leaving other proteins still bound and thus still masking thosesections of the nucleic acid molecule.

Binding proteins could be removed by the addition of a highconcentration of a competitor molecule. Such a molecule would contain abinding site for the particular protein to be removed. Affinity of thebinding site may be higher than that used in the template molecule ormerely by increasing the concentration of the competitor molecule, theprotein may be selectively removed from the template. The competitormolecule may be used in various forms, for example in solution, on asolid support, or attached to paramagnetic beads. The solid support orparamagnetic beads allows for the easy removal of much of the competitorDNA to allow the competitor DNA to be used in multiple reactions.Alternatively, when complete removal of competitor DNA is desired,nucleases can be used to digest the free DNA.

Proteins could also be removed from the nucleic acid molecule byaltering the temperature of the solution. Proteins lose their ability tomaintain their structure and activity at higher temperatures. Thus byincreasing temperature, proteins can be inactivated. However, iftemperature is used to remove proteins, care must be taken to designnucleic acid molecules so that the nucleic acid template will notdenature. Again differential release of proteins is possible usingchanges in temperature. Thermostable enzymes can be isolated fromcertain organisms. For instance, thermophilic bacteria produce proteins,which maintain their activity at temperatures above 80° C. Thus using amixture of proteins allows for the release of some proteins whilemaintaining the masking of other sites.

Temperature does denature nucleic acid sequences (Casey et al., Nucl.Acids Res. 4:1539 (1977), which is hereby incorporated by reference).Therefore, when using temperature to remove proteins from the nucleicacid molecule, the melting temperature of the nucleic acid moleculeshould be taken into account. The stability of the template may beimproved by ligating molecules nucleic acid molecules together.

Of course the removal of proteins can be facilitated by a combination ofvarious methods, such as altering both salt concentrations andtemperature (See e.g., Koblan et al., Biochem. 30:7817-21 (1991), whichis hereby incorporated by reference).

The negatively charged backbone of a nucleic acid molecule can be usedto attract and attach materials necessary to form circuit elements.Metals, doped metals, and other materials can be specifically bound toexposed regions of a DNA molecule.

For example, DNA can be used to form metal or metal composite wires(Braun et al., Nature 391:775 (1998), which is hereby incorporated byreference). Braun demonstrated that silver could be deposited along aDNA molecule. A three-step process is used. First, silver is selectivelylocalized to the DNA molecule through a Ag⁺/Na⁺ion-exchange (Barton, inBioinorganic Chemistry (eds Bertini, et al.) ch. 8 (University ScienceBooks, Mill Valley, 1994, which is hereby incorporated by reference) andcomplexes are formed between the silver and the DNA bases (Spiro (ed.)Nucleic Acid-Metal Ion Interactions (Wiley Interscience, New York 1980;Marzeilli, et al., J. Am. Chem. Soc. 99:2797 (1977); Eichorn (ed.)Inorganic Biochemistry, Vol. 2, ch 33-34 (Elsevier, Amsterdam, 1973),which are hereby incorporated by reference). The ion-exchange processmay be monitored by following the quenching of the fluorescence signalof the labeled DNA. The silver ion-exchanged DNA is then reduced to formaggregates with bound to the DNA skeleton. The silver aggregates arefurther developed using standard procedures, such as those used inphotographic chemistry (Holgate, et al., J. Histochem. Cytochem. 31:938(1983); Birell, et al., J. Histochem. Cytochem. 34:339 (1986), which arehereby incorporated by reference).

Chemical deposition of conductors, semi-conductors, or other materialscan be carried out using chemical techniques known in the art. As anexample, photographic dyes can be used with silver in knownphotochemical reactions. (James, The Theory of the Photographic Process4^(th) ed. (Macmillan Publishing, New York 1977), which is herebyincorporated by reference) Photographic dyes, like other solid organiccompounds containing π-electron chromophores, such as aromatichydrocarbons, are electronic semiconductors and photoconductors (James,The Theory of the Photographic Process, 4^(th) ed. (MacmillanPublishing, New York 1977); Kallman et al. eds., Symposium on ElectricConductivity of Organic Solids (Wiley-Interscience 1961); Meier, DiePhotochemie der Organischen Farbstoffe (Springer, Berlin 1963); Gutmanet al., Organic Semiconductors (Wiley, New York 1967); Meier, SpectralSensitization (Focal Press, London and New York 1968), which are herebyincorporated by reference).

Examples of suitable dyes which can be used as semiconductors have beenreviewed in Hamer, The Chemistry of Heterocyclic Compounds, Vol. 18, TheCyanine Dyes and Related Compounds, Weissberger, ed., Interscience, NewYork, 1964; Mees et al., eds. The Theory of the Photographic Process4^(th) Ed. (Macmillan, New York 1977); Ficken, The Chemistry ofHeterocyclic Compounds, Vol. 4, Venkataraman, ed. (Academic Press, NewYork 1971); and Sturmer, The Chemistry of Heterocyclic Compounds, Vol.30, Weissberger et al., ed. (John Wiley, New York 1977), which arehereby incorporated by reference). Preferred dyes include cyanine andmerocyanine dyes. Methods of synthesis for these compounds are wellknown in the art. Brooker et al., J. Am. Chem. Soc. 73:5326 (1951);Dimroth, et al., Justus Liebigs Ann. Chem. 373 (1975); Brooker et al.,J. Franklin Inst. 219:255 (1935); Brooker et al., J. Am. Chem. Soc.57:2480 (1935); Malhotra et al., J. Chem. Soc. 3812 (1960), which arehereby incorporated by reference). Sensitizing dyes adsorb to silverhalides (Herz, The Theory of the Photographic Process 4^(th) Ed. Chap.9, (Macmillan, New York 1977), which is hereby incorporated byreference). Thus dyes may be applied to the nucleic acid moleculesupport to produce semiconductor regions.

Metals or other materials once deposited may be doped through a varietyof techniques. In one embodiment, the doping material is mixed with themetal or other material in solution to form a doped compound on thenucleic acid substrate. In another embodiment, one or materials areapplied to the nucleic acid substrate and then the substrate is removedfrom solution and the material-substrate complex is exposed to dopingagents in a gaseous state. Additional materials may then be applied tothe nucleic acid substrate in additional steps.

Other positively charged ions could be deposited along a nucleic acidmolecule in a similar manner. The use of a nucleic acid molecule as atemplate is not limited to silver, other metals can be substituted.Moreover, the invention is not limited to metals. Burroughes et al.Nature 347, 539 (1990), which is hereby incorporated by reference,discloses that DNA can be used as a template to fabricate apoly-(p-phenylene vinylene) (“PPV”) filament by attaching a positivelycharged pre-PPV polymer to the stretched DNA and treating it to form aphotoluminescent PPV wire.

To expand the range of materials which may be used to create circuitelements, positively charged groups may be complexed with othermaterials which would not normally interact with the nucleic acidmolecule. The positively charged group can interact with the negativelycharged nucleic acid molecule. Alternatively, desired materials may becomplexed with compounds which will intercalate with the stackedbase-pairs in the nucleic acid molecule. In a preferred embodiment, theintercalating agent is ethidium bromide. Intercalating molecules mayalso be used to alter the inherent conductivity or resistivity of thenucleic acid molecule (Meade, U.S. Pat. No. 5,770,369 (1998), which ishereby incorporated by reference).

In another embodiment, a polymer composition effective to bind, in asequence-specific manner to a target sequence of a duplexpolynucleotide, at least two different-oriented Watson/Crick base-pairsat selected positions in the target sequence may be used to targetmaterials to the nucleic acid molecules. The polymer compositionincludes an uncharged backbone with 5- or 6-member cyclic backbonestructures and selected bases attached to the backbone structureseffective to hydrogen bond specifically with different orientedbase-pairs in the target sequence (Summerton, et al., U.S. Pat. No.5,405,938 (1995), which is hereby incorporated by reference).

In addition, during development, mixtures of metals may be used todeposit an alloy or doped material. Doping materials may be applied in aliquid state during development. The conductivity of the material mayalso be altered by heat treatment. Accordingly, the physical propertiesof the coating materials may be altered to produce desired electricalcharacteristics.

Once a material is deposited on the nucleic acid molecule, the nucleicacid molecule can be disrupted and /or removed by using treatments whichwill specifically disrupt the nucleic acid molecule but not affect thecircuit elements. Nucleic acid molecules can be disrupted, or possiblyremoved, by treating the circuit with nucleases, ionizing radiation,oxidizing compounds. In a preferred embodiment of the invention, nucleicacid molecules are disrupted by ionizing radiation.

As discussed above, the nucleic acid molecule may be modified prior tothe depositing of the coating material. Such modifications may alsoaffect the electrical properties of the resulting material.

Portions of the nucleic acid molecule scaffolding may be used to holdthe scaffolding in a particular arrangement. After metals or othermaterials are applied which will stabilize the structure, those segmentsof the nucleic acid molecules not needed in the circuit may be removed.Restriction endonucleases can be utilized to cut exposed nucleic acidmolecules in a sequence dependent manner (Short Protocols in MolecularBiology, A Compendium of Methods from Current Protocols in MolecularBiology, Ausubel, F. M., et al., editors, 2nd Edition, Green PublishingAssociates and John Wiley and Sons, New York (1992); Sambrook et al.,Molecular Cloning: a Laboratory Manual, Cold Spring Harbor, N.Y., ColdSpring Harbor Laboratory, (1989), which are hereby incorporated byreference). Double- and single stranded nucleases may be used to digestaway undesired portions of the nucleic acid molecules which are notprotested by metal, other materials, or binding proteins.

Conditions may be adjusted to give a high level of fidelity in theself-assembly of a computer circuit. However, some error may occur. Toovercome the occurrence of errors one may test the circuits producedusing presently available techniques to identify those circuits whichare correctly formed.

In addition, circuits may be designed so that the programming canidentify errors and compensate for malformed elements. For example,parallel circuit systems can be designed which allow for a wide range ofcomputational architectures. (See e.g., Bruck et al., U.S. Pat. No.5,280,607, “Method and Apparatus for Tolerating Faults in MeshArchitectures” (1991), which is hereby incorporated by reference).Defect tolerant architectures can be created by incorporating a highcommunication bandwidth. The high bandwidth enables the software toroute around defects (Heath et al., “A Defect-Tolerant ComputerArchitecture: Opportunities for Nanotechnology,” Science 280:1716(1998); Eaton et al., U.S. Pat. No. 4,939,694, “Defect TolerantSelf-Testing Self-Repairing Memory System” (1990), which are herebyincorporated by reference). Configuarable computing systems are reviewedin Villasenor et al., Scientific American 276:68 (1997), which is herebyincorporated by reference.

The circuit elements of the present invention may be combined withtraditional chip technology. Nucleic acid molecules can be readilyattached to wafers thus directing the attachment of nucleic acidmolecule based circuit elements. (Fodor et al., U.S. Pat. No. 5,445,934,“Array of Oligonucleotides on a solid surface” (1995), which is herebyincorporated by reference). Such wafers may even be used as a substratein the formation of nucleic acid based circuits. Alternatively, thecircuits may be formed and then connected to nucleic acid molecules on awafer to integrate the nucleic acid based circuits into conventionalsystems.

Once the circuit is produced, it may be encapsulated in a non-conductivematerial to protect the circuit from damage. Preferred encapsulatingagents would be plastics or glass-like materials.

The method of the present invention can be used to manufactureintegrated circuits and the elements which make up integrated circuits,including, transistors, resistors, capacitors, inducers, and diodes. Thecircuit elements can be arranged to create logic circuits and otherelectronic circuits (Marston, Digital Logic IC Pocketbook (Reed ElsevierPub., Boston 1996), which is hereby incorporated by reference).

The present invention can be used to build integrated circuits or toattach circuit elements to circuits made by existing technologies. Inparticular the invention is useful for making elements in threedimensions, something which is costly or sometimes impossible to do withconventional chip technologies. The invention may also be used to makenano-scale containers for drugs or other materials. The composition ofthe shell could be varied to control the release of the material fromthe container. The invention could also be made to construct nano-scalemechanical or structural components for various devices, rather thanmachining such small devices. The present invention allows for a rapidand inexpensive method for making

EXAMPLES Example 1 Resistor

In one embodiment of the present invention, the method is used to createa resistor. FIG. 1 depicts the synthesis of a resistor element. On ormore binding molecules are incubated in solution with a DNA scaffoldingprotein having the binding site for the binding molecule. After thebinding molecule binds to the site, silver is applied to the unprotectedregions of the DNA scaffolding molecule. The silver is only laid down onregions where the negatively charged DNA backbone is accessible. Thisstep creates a silver wires leading up to both sides of the protectedregion. The binding molecule is then removed from the region and adifferent metal, doped metal or other conductive material is laid downover the protected region. The other metal, doped metal, or otherconductive material has a different resistance. The strength of theresistor can be varied by varying the size of the region protected bythe binding molecules.

Example 2 A Diode

Diodes consist of a p and an n type semiconductor. Since current canonly flow from the p to n region, diodes limit the flow of current inone direction. Diodes are useful for the conversion of AC current to DCcurrent.

Diodes can be readily assembled using the present invention. FIG. 2summarizes the synthesis of a diode. The process is similar that used tomake a resistor, except that two different binding proteins can be usedto protect contiguous sites. A wire is laid down over the remainder ofthe nucleic acid molecule. If necessary, a protective coating is appliedto the wire. One of the nucleic acid binding proteins is removed fromthe nucleic acid molecule. A competing nucleic acid molecule with thebinding site for the first binding protein may be used in a highconcentration to compete off the first binding protein with littleeffect on the second binding protein. A p or n semiconductor is thenapplied to the exposed portion of the nucleic acid molecule. Again, aprotective coating may be applied to the applied material. The secondnucleic acid binding molecule is then removed and the n or psemiconductor, opposite that which was previously applied, is applied tothe newly exposed portion of the nucleic acid molecule.

Furthermore, diodes and transistors may be assembled concurrently if thesame materials are used for the p and n semiconductors for bothelements.

Example 3 A Transistor

In order to make the necessary template, two nucleic acid molecules areselected where the first nucleic acid molecule can hybridize to acentral portion of the second nucleic acid molecule. FIG. 3 summarizesone method for the synthesis of a transistor using a nucleic acidmolecule substrate. Nucleic acid binding proteins are selected which canbind the central region. Proteins which bind specifically to X and Ynucleic acid structures are known in the art (See Elborough, et al.,“Specific Binding or Cruciform DNA Structures by a Protein from HumanExtracts,” Nucl. Acids Res. 16:3603-16 (1988); Chan et al., “Recognitionand Manipulation of Branched DNA by the RusA Holliday Junction Resolvaseof Escherichia coli,” Nucl. Acids Res. 26:1560-66 (1998); which arehereby incorporated by reference). A second binding protein is used toprotect two branches of the nucleic acid molecule adjacent to thejunction binding protein. Silver wiring is deposited and the protectingmolecule is removed. The junction binding protein is selectively removedfrom the nucleic acid molecule. This exposes a region in the middle ofthe previously protected region and is bound to the nucleic acidtemplate (FIG. 3D). Either a p or n type material is deposited onto theunprotected and exposed portions of the DNA molecule (FIG. 3E). Theother protecting molecules are then removed (FIG. 3F) and the exposedregion is then filled in with an n or p type material to complete thetransistor (FIG. 3G).

Example 4 An Inducer

Inducers produce a magnetic field which can induce a current in a nearbypart of the circuit. Inducers are used as transformers to change voltagein a circuit. Inducers are also important in the formation of radioreceivers. Inducers are usually formed of a coil of a conductivematerial. Current moving around the coil produces a magnetic field.However, a coil structure, since it is three dimensional, cannot beproduced on traditional semiconductor chips.

Inducers can be produced using the present invention. One method forproducing inducers relies on the use of histone-like proteins.Histone-like proteins are DNA binding proteins which are involved in theformation of nucleosomes (Wolffe, “Histone H1,” Int. J. Biochem. CellBiol. 29:1463-66 (1997); Zhang et al., “Characteristics of a Chlamydiapsittaci DNA binding Protein (EUO) Synthesized During the Early andMiddle Phases of the Developmental Cycle,” Infect. Immun. 66:1167-73(1998); Dutnall, et al., “Twists and Turns of the Nucleosome: TailsWithout Ends,” Structure 5:1255-59 (1997); Wintjens et al., “StructuralClassification of HTH DNA Binding Domains and Protein-DNA InteractionModes,” J. Mol. Biol. 262:294-313 (1996); Staynov, et al., “Footprintingof Linker Histones HS and Hi on the Nucleosome,” EMBO J. 7:3685-91(1988); which are hereby incorporated by reference). The DNA moleculewraps around the histone protein forming a compact coil. To produce aninducer, a nucleic acid molecule is wrapped around one or more histoneproteins. After the nucleic acid molecule is formed into a coil, a metalor other conductive material is applied to the DNA, as discussed above.

After the nucleic acid molecule wraps around the histone protein, aconductive material is applied to the nucleic acid molecule. The histoneprotein may be removed later by chemical digestion.

Example 5 Capacitor

A capacitor comprises a pair of conductive layers separated by adielectric layer. As with other electric circuit elements, DNA moleculescan be used to direct the synthesis of a capacitor by directing theplacement of conductive materials and /or the dielectric materials. FIG.5 shows one approach using two DNA molecules held parallel to eachother. The parallel DNA fragments (A) are coated in a conductivematerial and are connected to leads (B), which may or may not containDNA. The leads or the parallel wires may be connected to a conventionalelectronic circuit. Additional DNA molecules are used as spacers (C) toposition the templates, which will be coated with a conductive material.These spacers are protected prior to deposition of the conductivematerial. After coating, the spacers may be exposed, then cut withrestriction enzymes and removed. The resulting conductive wires arepositioned parallel to one another. The dielectric material can be air.Alternatively, the parallel conductors can be immersed in an alternativedielectric material.

In an alternative approach, the DNA templates can be used to form adielectric material between the conductive wires. Additional DNAfragments would be used which would hold additional fragments betweenthe fragments, which are to be coated with a conductor. The fragments tobe coated with the dielectric or those to be coated with the conductorwould be protected while the other fragments are coated then thefragments would be exposed and coated with the second material. Thespacer fragments, which are protected with a different protectivematerial, would then be exposed and removed if desired.

Although preferred embodiments have been depicted and described indetail herein, it will be apparent to those skilled in the relevant artthat various modifications, additions, substitutions, and the like canbe made without departing from the spirit of the invention and these aretherefore considered to be within the scope of the invention as definedin the claims which follow.

What is claimed is:
 1. A circuit element comprising: a nucleic acidtemplate; two or more sequential regions along a length of the templateare coated with different materials, wherein each of the differentmaterials is at least partially conductive.
 2. The circuit elementaccording to claim 1 wherein each of the different materials has adifferent resistivity from the other.
 3. The circuit element accordingto claim 1 wherein each of the different materials is a dopedsemiconductor material.
 4. The circuit element according to claim 3wherein the doped semiconductor material is either an n-type or a p-typesemiconductor material.
 5. The circuit element according to claim 1wherein the nucleic acid template is DNA.
 6. The circuit elementaccording to claim 1 wherein the nucleic acid template is RNA.
 7. Aresistor comprising a first material separated by a second material, thesecond material having a different resistivity than the first materialand the first and second materials having a common nucleic acid templatecore.
 8. The resistor according to claim 7 wherein the first materialcomprises metal and the second material comprises an at least partiallyconductive material.
 9. The resistor according to claim 7 wherein thenucleic acid template is DNA.
 10. The resistor according to claim 7wherein the nucleic acid template is RNA.
 11. A resistor comprising: atleast one resistive material; and a pair of at least partiallyconductive leads, each of the leads coupled to the resistive material;the resistive material and the pair of leads having a nucleic acidtemplate core.
 12. The resistor according to claim 11 wherein each ofthe pair of leads is made at least one metal material which coats aregion of the nucleic acid template core.
 13. The resistor according toclaim 11 wherein the nucleic acid template is DNA.
 14. The resistoraccording to claim 11 wherein the nucleic acid template is RNA.
 15. Adiode comprising a first type of semiconductor material adjacent to asecond type of semiconductor material, the first and second types ofsemiconductor materials having a common nucleic acid template core. 16.The diode according to claim 15 wherein the first and second types ofsemiconductor materials are N-type and P-type semiconductor materials.17. The diode according to claim 15 further comprising a pair of atleast partially conductive leads, each of the leads coupled to one ofthe first and second types of semiconductor materials and having thecommon nucleic acid template core.
 18. The diode according to claim 15wherein the nucleic acid template is DNA.
 19. The diode according toclaim 15 wherein the nucleic acid template is RNA.
 20. A diodecomprising: a first type of semiconductor material; a second type ofsemiconductor material adjacent to the first type of semiconductormaterial; and a pair of at least partially conductive leads, each of theleads coupled to one of the first and second types of semiconductormaterials; the first and second types of semiconductor materials and thepair of leads having a nucleic acid template core.
 21. The diodeaccording to claim 20 wherein the first and second types ofsemiconductor materials are N-type and P-type semiconductor materials.22. The diode according to claim 20 wherein the nucleic acid template isDNA.
 23. The diode according to claim 20 wherein the nucleic acidtemplate is RNA.
 24. A capacitor comprising a pair of at least partiallyconductive plates separated by a dielectric, each of the plates having anucleic acid template core.
 25. The capacitor according to claim 24further comprising a pair of at least partially conductive leads, eachof the leads coupled to one of the plates.
 26. The capacitor accordingto claim 24 wherein the nucleic acid template is DNA.
 27. The capacitoraccording to claim 24 wherein the nucleic acid template is RNA.
 28. Acapacitor comprising a pair of at least partially conductive platesseparated by a dielectric, the dielectric having a nucleic acid templatecore.
 29. The capacitor according to claim 24 wherein the dielectric isair.
 30. The capacitor according to claim 28 wherein the nucleic acidtemplate is DNA.
 31. The capacitor according to claim 28 wherein thenucleic acid template is RNA.
 32. A transistor comprising a first typeof semiconductor material separated by a second type of semiconductormaterial, the first and second types of semiconductor materials having acommon nucleic acid template core.
 33. The transistor according to claim32 wherein the first and second types of semiconductor materials areN-type and P-type semiconductor materials.
 34. The transistor accordingto claim 32 wherein the nucleic acid template core comprises threebranches having a common intersection, the second type of semiconductormaterial coating at least a portion of the common intersection and thefirst type of semiconductor material coating at least a portion of twoof the three branches adjacent the intersection.
 35. The transistoraccording to claim 34 further comprising a plurality of at leastpartially conductive leads, each of the leads coupled to one of thefirst and second types of semiconductor materials along one of the threebranches and having the common nucleic acid template core.
 36. Thetransistor according to claim 32 wherein the nucleic acid template isDNA.
 37. The transistor according to claim 32 wherein the nucleic acidtemplate is RNA.
 38. A transistor comprising: a first type ofsemiconductor material; a second type of semiconductor materialseparating the first type of semiconductor material; and a plurality ofat least partially conductive leads, each of the leads is coupled to oneof the first and second types of semiconductor materials; the first andsecond types of semiconductor materials and the leads having a nucleicacid template core.
 39. The transistor according to claim 38 wherein thenucleic acid template core comprises three branches having a commonintersection, the second type of semiconductor material coating at leasta portion of the common intersection and the first type of semiconductormaterial coating at least a portion of two of the three branchesadjacent the intersection.
 40. The transistor according to claim 39wherein each of the leads is coupled to one of the first and secondtypes of semiconductor materials along one of the three branches. 41.The transistor according to claim 38 wherein the first and second typesof semiconductor materials are N-type and P-type semiconductormaterials.
 42. The transistor according to claim 38 wherein the nucleicacid template is DNA.
 43. The transistor according to claim 38 whereinthe nucleic acid template is RNA.
 44. An inducer comprising a coil of atleast partially conductive material, the coil of at least partiallyconductive material having a nucleic acid template core.
 45. The induceraccording to claim 44 further comprising a core structure, the coil ofat least partially conductive material wrapped at least partially aroundthe core.
 46. The inducer according to claim 45 wherein the corestructure comprises a histone-like protein.
 47. The inducer according toclaim 44 wherein the nucleic acid template is DNA.
 48. The induceraccording to claim 44 wherein the nucleic acid template is RNA.
 49. Amethod for making a resistor, the method comprising: protecting at leastone region of a nucleic acid molecule template using a nucleic acidbinding molecule; coating unprotected regions of the nucleic acidmolecule template with a first conductive material; removing the nucleicacid binding molecule from the protected region; and coating theprotected region with a second conductive material, where the secondconductive material has a different resistivity from the firstconductive material.
 50. The method according to claim 49 wherein thenucleic acid template is DNA.
 51. The method according to claim 49wherein the nucleic acid template is RNA.
 52. A method for making adiode, the method comprising: protecting at least one region of anucleic acid molecule template using two or more nucleic acid bindingmolecules; coating unprotected regions of the nucleic acid moleculetemplate with a conductive material, removing at least one of thenucleic acid binding molecules from one portion of the protected region;coating the one portion of the protected region with a first-type ofsemiconductor material; removing any remaining ones of the nucleic acidbinding molecules from any remaining portion of the protected region;and coating the remaining portion of the protected region with a secondtype of semiconductor material.
 53. The method according to claim 52wherein the first and second types of semiconductor materials are N-typeand P-type semiconductor materials.
 54. The method according to claim 52wherein the nucleic acid template is DNA.
 55. The method according toclaim 52 wherein the nucleic acid template is RNA.
 56. A method formaking a capacitor, the method comprising coating parallel regions of anucleic acid molecule template with a conductive material, each of thecoated parallel regions coupled to a lead.
 57. The method according toclaim 56 further comprising: protecting at least one spacer region ofthe nucleic acid molecule template using at least one nucleic acidbinding molecule; removing the nucleic acid binding molecule from theprotected spacer region after the coating of the parallel regions; andremoving the spacer region of the nucleic acid molecule template. 58.The method according to claim 56 wherein at least one of the parallelregions of the nucleic acid template is DNA.
 59. The method according toclaim 56 wherein at least one of the parallel regions of the nucleicacid template is RNA.
 60. A method for making a capacitor, the methodcomprising: protecting a first region of a nucleic acid moleculetemplate between parallel regions of a nucleic acid molecule templatewith at least one nucleic acid binding molecule; coating unprotectedparallel regions of the nucleic acid molecule template around the firstregion with a conductive material; removing the nucleic acid bindingmolecule from the first region; and coating the first region with adielectric material.
 61. The method according to claim 60 wherein atleast one of the parallel regions of the nucleic acid template is DNA.62. The method according to claim 60 wherein at least one of theparallel regions of the nucleic acid template is RNA.
 63. A method formaking a transistor, the method comprising: protecting a central regionand two of three adjacent branch regions of a nucleic acid moleculetemplate with nucleic acid binding molecules; coating unprotectedregions of the nucleic acid molecule template with a conductivematerial; removing the one or more nucleic acid binding moleculesprotecting the central region of the nucleic acid molecule template;coating the central region with a first-type of semiconductor material;removing the nucleic acid binding molecules from the protected branchregions; and coating the branch regions with a second type ofsemiconductor material.
 64. The method according to claim 63 wherein thefirst and second types of semiconductor materials are N-type and P-typesemiconductor materials.
 65. The method according to claim 63 whereinthe nucleic acid template is DNA.
 66. The method according to claim 64wherein the nucleic acid template is RNA.
 67. A method for making aninducer, the method comprising: wrapping a nucleic acid moleculetemplate around at least one protein; and coating the nucleic acidmolecule template with a first conductive material.
 68. The methodaccording to claim 67 wherein the protein comprises a histone-likeprotein.
 69. The method according to claim 67 wherein the nucleic acidtemplate is DNA.
 70. The method according to claim 67 wherein thenucleic acid template is RNA.